Pharmacokinetics: Plausible explanations for the increased requirement of LMWH per body weight in young children include altered heparin pharmacokinetics and/or a decreased expression of anticoagulant activity of heparin in children due to lower levels of AT.
Monitoring: Nomograms for the adjustment of therapeutic doses of LMWH have been validated (Table 5).
Treatment of LMWH-lnduced Bleeding: If anticoagulation with LMWH needs to be discontinued for clinical reasons, termination of the subcutaneous injections will usually suffice. If an immediate effect is required, protamine sulfate has not been shown to completely reverse LMWH. Equimolar concentrations of protamine sulfate neutralize the anti-factor Ha activity but result in only partial neutralization of the anti-factor Xa activity. In animal models, however, bleeding is completely reversed by protamine sulfate. The dose of protamine sulfate is dependent on the dose of LMWH used at the time of administration other canadian healthcare mall. If protamine is given within 3 to 4 h of the LMWH, then a maximal neutralizing dose is 1 mg of protamine per 100 U (1 mg) of LMWH given in last-dose IV over 10 min. The same instructions for protamine sulfate administration for the reversal of heparin should be followed (Table 3).
Initial studies suggested that LMWH would cause less bleeding than unfractionated heparin for a similar antithrombotic effect. A review of clinical studies to date, however, has failed to substantiate that claim. The FDA recently issued a warning concerning the danger of spinal hematoma occurring in adult patients undergoing epidural or lumbar punctures while receiving LMWH. Preliminary studies show that a significant proportion of children have substantial anti-factor Xa plasma activity 12 h following a subcutaneous treatment dose of LMWH. Further studies are required to determine the true bleeding risk from LMWH in children. Until such evidence is available, the risk of bleeding complications from LMWH should be considered to be similar to unfractionated heparin for the equivalent antithrombotic effect. In particular, prior to lumbar punctures or epidural procedures, at least 2 doses of LMWH should be withheld and, if possible, anti-factor Xa levels should be determined prior to the procedure.
Table 5—Nomogram for Monitoring Reviparin/Enoxaparin in Pediatric Patients
|Anti-Factor Xa Level||Hold Next Dose?||Dose Change?||Repeat Anti-Factor Xa level?|
|<0.35 U/mL||No||Increase by 25%||4 h after next dose|
|0.35-0.49 U/mL||No||Increase by 10%||4 h after next dose|
|0.5-1.0 U/mL||No||No||Next day, then 1 wk later and monthly thereafter while receiving Reviparin-Na treatment (at 4 h after AM dose)|
|1.1-1.5 U/mL||No||Decrease by 20%||Before next dose|
|1.6-2.0 U/mL||3 h||Decrease by 30%||Before next dose, the 4 h after next dose|
|>2.0 U/mL||Until anti-Xa 0.5 U/mL||Decrease by 40%||Before next dose, if not <0.5 U/mL, repeat ql2h|